Coronary partial stenosis creates primarily subendocardial ischemia in the dog, while perfusion in outer myocardial layers may remain normal, but the functional significance of sustained blood flow in the outer myocardial layers is not clear. It is proposed to examine the effect of ischemia on wall thickening dynamics by creating graded coronary stenoses; regional myocardial blood flow measurements will be correlated with systolic wall thickening. An experimental approach is proposed to simultaneously measure systolic performance in the superficial and deep myocardium by measuring systolic thickening of the total wall and outer half of the wall in closely adjacent locations. First, the responses of the total wall and the outer half of the wall to interventions (intravenous isoproterenol and lidocaine), designed to stimulate or depress the myocardium transmurally, will be documented to test the hypothesis that both halves of the wall respond in parallel during conditions in which transmural perfusion is uniform. Experiments will then be performed in which subendocardial ischemia (i.e. nonuniform transmural perfusion) is created using coronary stenosis to test the hypothesis that outer wall systolic thickening will be markedly reduced by ischemia limited to the underlying muscle. To test the hypothesis that outer myocardial function is limited by the counteractive force generated by nonischemic myocardium, global ischemia will be produced to eliminate the imbalance between ischemic and nonischemic myocardial contractile forces postulated to exist during conditions of regional ischemia. In addition, a conscious animal preparation is proposed to address how regional flow-function relations change with time after myocardial infarction. Long-term adjustments to chronic myocardial ischemia may include substantial changes in the contractile function of the viable subepicardial layers which, we propose, improves with time thereby greatly modifying the relationship between regional wall thickening and blood flow observed acutely.